Abstract

Background

In recurrent malignant gliomas (MGs), a high rate of haematological toxicity is observed
with the use of fotemustine at the conventional schedule (100 mg/m2 weekly for 3 consecutive weeks followed by triweekly administration after a 5-week
rest period). Also, the impact of O6-methylguanine-DNA methyltransferase (MGMT) promoter
methylation status on fotemustine activity has never been explored in the clinical
setting.

Methods

40 patients with recurrent pretreated MG were identified as being treated with fotemustine
at doses ranging from 65 mg/m2 to 100 mg/m2. Patients were classified into 3 groups according to the dose of fotemustine received,
from the lowest dosage received in group A, to the highest in group C. Analysis of
MGMT promoter methylation in tumor tissue was successfully performed in 19 patients.

Results

Overall, 20% of patients responded to treatment, for a disease control rate (DCR,
responses plus stabilizations) of 47.5%. Groups A and B experienced a response rate
of 40% and 26.5% respectively, while the corresponding value for group C was 10%.
Out of 19 patients, MGMT promoter was found methylated in 12 cases among which a DCR
of 66.5% was observed. All 7 patients with unmethylated MGMT promoter were progressive
to fotemustine.

Conclusion

Low-dose fotemustine at 65–75 mg/m2 (induction phase) followed by 75–85 mg/m2 (maintenance phase) has an activity comparable to that of the conventional schedule.
By determination of the MGMT promoter methylation status patients might be identified
who are more likely to benefit from fotemustine chemotherapy.